This application claims priority under 35 U.S.C. xc2xa7xc2xa7 119 and/or 365 to 10100984.4 filed in Germany on Jan. 10, 2001; the entire content of which is hereby incorporated by reference.
1. Field Of The Invention
The invention relates to an apparatus to calibrate multi-channel pipettes by means of a measuring device, and it also relates to a device for transporting receptacles containing a test liquid to a measuring device.
2. Background Information
Pipettes are instruments for transferring defined amounts of liquids from one container to another and are used in particular in laboratories. The dispensing of liquids by means of pipettes is often the first step in a series of analytical experiments. Multi-channel pipettes are particularly efficient to work with, because they allow liquid to be aspirated simultaneously from one or more containers and to be dispensed into several receptacles at once. It is of particular importance that the volume of liquid taken in and dispensed to other containers is the same in all channels. In view of the strict requirements on the accuracy of the transferred volume, pipettes used for the foregoing purpose, especially multi-channel pipettes, have to be tested several times in the course of a year. In addition, verification tests of pipettes are required under official guidelines and international standards. A verification test is often referred to as a calibration.
For example, piston pipettes with an air cushion, in volume sizes above one microliter, can be calibrated by a gravimetric method, normally using distilled water as test liquid and calculating the volume from the weight and density of the water held by the pipette. Environmental factors including temperature, barometric pressure and relative humidity of the air are taken into account in the volume calculation. The specifics of the gravimetric test method are described, e.g., in the draft standards pr-EN 8655 or ISO/DIS 8655, part 6. In variable-volume pipettes, the test is performed at 100%, 50%, and at a smaller volume of at least 10% of the nominal capacity. For a complete calibration test according to the standard, a series of at least ten consecutive measurements has to be performed at each of the tested volumes. To test a multi-channel pipette, pr-EN 8566 or ISO/DIS 8655, part 6, section 7.3, requires that all channels must be filled with the test liquid, but only the liquid in the channel that is currently being tested is dispensed into the recipient container (also referred to as receptacle) on the load receiver of a weighing device. In other words, each channel has to be measured individually. In a more extensive procedure which is also described in the aforementioned standards and requires 30 measurements in a single-channel pipette, the calibration test of a multi-channel pipette with, e.g., 12 channels requires 360 cycles of aspirating, dispensing and weighing, so that the test can take several hours, especially if more than one volume is to be tested in a multi-channel, variable-volume pipette.
A gravimetric test apparatus for multi-channel pipettes is described in the German utility model DE U1 299 17 940, in which a separate receiving device is provided for each pipette channel (with a minimum of two), and a separate weighing cell is provided for each receiving device. In other words, the apparatus has a separate weighing cell for each pipette channel. For a 12-channel pipette, this concept would require 12 weighing cells.
The foregoing arrangement for a gravimetric test apparatus for multi-channel pipettes has the disadvantage that it requires more than one weighing cell, i.e., as many weighing cells as there are pipette channels, where each of the weighing cells would also have to be calibrated. Thus, the concept is very expensive to put into practice. As a further disadvantage, the weighing cells have to be arranged relatively close to each other. This limits the level of accuracy that can be achieved, because for the weighing cells to be compact enough, they would have to be strain-gauge load cells, which will not in all cases have the accuracy required for the calibration of pipettes. It is furthermore hard to avoid that the heat build-up and heat flow in a close aggregation of weighing cells can cause temperature gradients that are detrimental to the weighing accuracy. The foregoing concept of multiple weighing cells could be realized with electromagnetic compensation cells, but the latter would have to be arranged farther apart from each other than would be compatible with the distance of the receptacles when they are filled by dispensing the liquid from the channels of the pipette. Thus, the receptacles would have to be moved to the respective load receivers, which would require a complex system of rods and levers. The higher accuracy available with multiple electromagnetic compensation cells thus comes at a high cost due to the complexity of monitoring and calibrating the multiple weighing cells.
The present invention therefore has the objective of providing an apparatus for the gravimetric calibration of multi-channel pipettes with a transport device that advances the receptacles to the measuring device. The apparatus should have an uncomplicated design that causes no loss of precision of the calibration measurements, can be realized at a favorable cost, and has a faster operating speed, so that a multi-channel pipette can be calibrated in a reasonable amount of time.
An apparatus for the gravimetric calibration of multi-channel pipettes according to the present invention contains a balance that has a load receiver configured to support receptacles containing a substance to be weighed. The apparatus has a holder device to support a certain number of the receptacles into which a test liquid is dispensed from the multi-channel pipette. The apparatus further has a transport device for advancing the holder device towards the load receiver. The receptacles are seated in the holder device at equally spaced positions with a defined distance from each other. The transport device has means whereby one after another of the receptacles can be delivered to and subsequently removed from the measuring device.
Because the apparatus according to the invention contains only one balance, it represents a more cost-effective solution. Due to its uncomplicated design, the apparatus also takes up less space than known state-of-the-art arrangements. With the need for only one balance, it is possible to use a high-precision balance that is equipped with one of the known self-calibration mechanisms and meets the stringent requirements described in the standards for calibrating multi-channel pipettes. The transport device and/or the holder device are designed to precisely position the receptacles on the load receiver. The apparatus according to the invention can be offered either as an accessory to a high-precision analytical balance of a standard model version, or it can also be offered as an integrated system.
In a preferred embodiment of the invention, the transport device is encased in a housing, with the balance also installed in the same housing. The load receiver is arranged on top of the balance and extends upwards into the holder device through an opening of the housing. The load receiver has two lateral wing portions with indentations at their upper ends for the positive positioning of the suspended receptacle.
In an advantageous embodiment of the invention, the defined distance between the receptacles in the holder device corresponds to the spacing of the tips of a multi-channel pipette that is to be calibrated, and the number of the receptacles in the holder device is not less than the number of pipette tips.
The transport device for advancing the holder device to the load receiver can be used for applications other than the calibration of multi-channel pipettes. The capability to transport receptacles in a holder device to a measuring device would also be useful, e.g., with a spectrometer.
The transport device is equipped with a holder device for receptacles that can be filled with a liquid or a pourable solid substance. The arrangement of the receptacles in the holder device is such that they center themselves and can be individually handled. The holder device is designed to be moved in the transport device and has means for damping the movement of the receptacles if an external influence displaces them from their rest positions. The transport device is equipped to deliver the receptacles one by one to the measuring device. In the same movement as one receptacle is removed from the measuring device, a next following receptacle is delivered to the measuring device.
The receptacles can have a round, oval or rectangular cross-section. When seated in the holder device, they are equally spaced at a defined distance from each other. At its top end, each receptacle has a pair of rigid horizontal suspension members by which the receptacles are suspended in indentations of a holder rack in the holder device.
In a preferred embodiment, the suspension members consist of rod members attached to the receptacles by sockets that partially embrace the circumference of the receptacle. The rod members have inward-pointing cones at their far ends, and at least one of each pair has a double cone, i.e., two cones joined at their bases and pointing away from each other. A ring groove is formed where the tip of the inward-pointing cone meets the outward-pointing tip of the double cone. The ring groove serves to define the seating position of the suspension member in the indentation of the holder rack.
In a particularly advantageous embodiment of the invention, the holder device is designed so that it can be separated from the transport device.
The holder device has a cover to avoid contamination and reduce evaporation of the liquid in the receptacles. In addition, the holder device has at least one tub located near the fill openings of the receptacles. The tubs can be filled with the test liquid which, by evaporating and saturating the atmosphere inside the holder device, will further contribute to reducing the evaporation of the test liquid from the receptacles. The underside of the holder device is designed to keep out air circulation when the holder device is set down on a flat surface, and particularly to prevent air drafts from reaching the load receiver of the analytical balance when the apparatus is used for pipette calibration.
In a further developed advantageous embodiment, the transport device is designed to perform a combined movement where the holder device is moved horizontally forward or backward while being simultaneously raised and lowered. The drive mechanism for the combined movement works with a single motor that is provided in the transport device.
An advantageous embodiment of the invention provides for a transport carriage that moves in a transport channel of the transport device and has a seat to receive the holder device. The movement of the transport carriage in the transport device is guided by at least one transport rack that is part of the transport device. Also, the transport device is preferably equipped with a position sensor to detect the actual position of the holder device or of the transport carriage within the transport device.
In a preferred embodiment, the transport device is encased in a housing, and the drive mechanism is attached to the housing. The drive mechanism has a drive wheel with at least two bolts or rollers. A drive rack with arcuate cutouts is attached to either the transport carriage or the holder device. The bolts or rollers of the drive wheel engage the cutouts of the drive rack so that, when the drive wheel turns, the holder device is moved along the transport channel. The drive rack, the transport rack, as well as the holder rack of the holder device are shaped with the same periodic pitch.
The holder device can be guided by the transport device on a linear or circular path. In the latter case, the holder device could also be of a circular design in the manner of a carousel holder.
In a further developed embodiment of the invention, the receptacles are marked with a code, e.g., at the bottom of the receptacle. The transport device is suitably equipped with a sensor head and with a means of transmitting the coded information from the receptacle bottom to the sensor head. In addition, or as an alternative, the holder device can be marked with a code which can be read by a sensor device that is mounted on the transport device at the same level as the code marking on the holder device.
Further details of the design and function of the inventive apparatus for the gravimetric calibration of multi-channel pipettes and of the transport device for transporting receptacles to a measuring device may be learned from the following description of a preferred embodiment that is represented schematically in the drawings.